Reading a binary file in Python: takes a very long time to read certain bytes?

Although it's hard to say without some kind of reproducible sample, this sounds like a buffering problem. The First part is buffered and until you reach the end of the buffer, it is fast; then it slows down until the next buffer is filled, and so on.

When lists/dicts/whatever get very large there can be a noticeable delay when they need to be reallocated and resized.

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